Teratogenicity of high vitamin A intake.
Level 3 - non-randomized controlled study
Prospective observational cohort study
PubMed 7477116 · doi:10.1056/NEJM199511233332101
What was done
A prospective cohort of 22,748 pregnant women undergoing prenatal screening (maternal serum alpha-fetoprotein or amniocentesis) was enrolled between October 1984 and June 1987. Nurse interviewers recorded diet, supplement use, medications, illnesses during the first trimester, family and medical history, and environmental exposures. Pregnancy outcomes and birth defects were collected from delivering obstetricians or the women themselves.
What was found
Of 22,748 women, 339 had babies with birth defects, including 121 with cranial neural crest defects. For cranial-neural-crest defects, the prevalence ratio comparing preformed vitamin A intake over 15,000 IU per day from food and supplements combined to 5,000 IU per day or less was 3.5 (95 percent confidence interval, 1.7 to 7.3). For supplemental vitamin A alone, the prevalence ratio for intake over 10,000 IU per day versus 5,000 IU per day or less was 4.8 (95 percent confidence interval, 2.2 to 10.5). A smoothed regression curve indicated an apparent threshold near 10,000 IU per day of supplemental vitamin A, with increased risk concentrated before the seventh week of gestation. The authors estimated that approximately 1 in 57 infants born to women taking over 10,000 IU per day in supplements had an attributable defect.
Why it matters
This study provided pivotal epidemiological evidence identifying a teratogenic threshold for high preformed vitamin A intake during human embryogenesis, defining safe limits for prenatal supplementation.
Limits
Exposure assessment relied on maternal self-report and dietary recall. The cohort was restricted to women undergoing specific prenatal screening procedures. Circulating serum retinol or retinoid metabolite levels were not measured.
Cited by
- supports Eating liver is restricted during pregnancy because high levels of vitamin A can cause developmental harm to the fetus.